The food borne pathogen Campylobacter jejuni (CJ) causes between 2.5 and 3 million human disease cases and approximately 100 deaths annually at an estimated cost of between 1.6 and 6.2 billion dollars. Poultry is the major reservoir for human disease caused by CJ. Our long term goal is to prevent human illness by developing effective control strategies in two areas: a) bio-control agents to reduce disease reservoir development in poultry;b) enhance innate or adaptive immunity to reduce human colonization. Previously we demonstrated that all CJ strains analyzed colonize Ross 308 broilers while only a small number of these strains colonize C57BL/6J IL10 (-/-) mice, our model for human disease. During colonization, CJ genetic diversity expands in the broiler GI tract while genetic diversity is severely reduced in the mouse GI tract. We also demonstrated that these two dissimilar methods of genetic adaptation promote subsequent colonization of mice by CJ. Our central hypothesis is that genetic adaptation in poultry plays a key role in the ability of CJ subsequently to colonize and cause disease in mice. To address this hypothesis, we will accomplish the following Specific Aims: 1) study the mechanisms for generating genetic diversity in broilers and mice by analyzing the frequency and pattern of mutation in contingency genes;2) block genetic adaptation in broilers and analyze the impact on subsequent ability to colonize and cause disease in mice. An understanding of CJ human disease reservoir development in poultry will result in a major positive impact on human illness associated with this food borne pathogen. PUBLIC HEALTH RELEVANCE: The food borne pathogen Campylobacter jejuni (CJ) causes between 2.5 and 3 million human disease cases and approximately 100 deaths annually at an estimated cost of between 1.6 and 6.2 billion dollars. Poultry is the major reservoir for human disease caused by CJ. Our long term goal is to prevent human illness by developing effective control strategies in two areas: a) bio-control agents to reduce disease reservoir development in poultry;b) enhance innate or adaptive immunity to reduce human colonization.